Spitz Tumors of the Skin

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Abstract

Spitz tumors are melanocytic neoplasms hallmarked by large cell size, lack of high-grade atypia, and a regular architecture. Most are nonpigmented or poorly pigmented. Malignant potential ranges from absent (Spitz nevus), to fully present (spitzoid melanoma), with a further, ill-defined group of Spitz tumors with limited metastatic potential. Microscopic evaluation may prove inconclusive in some instances, resulting in a verdict of Spitz tumor of uncertain malignant potential (STUMP). STUMP is, therefore, not an entity, and should not be equated with Spitz tumors with limited metastatic potential. Novel diagnostic techniques are yielding promising results, and further evaluation is ongoing.

Section snippets

Overview

Spitz nevus is a benign tumor of melanocytes, distinguished histologically by the large size of the neoplastic melanocytes, as well as several architectural features that to some degree resemble those of melanoma. As a result of these similarities, the histologic differential diagnosis between Spitz nevus and melanoma is a common source of diagnostic uncertainty and error. These diagnostic problems are compounded by the occurrence of a small group of melanomas (referred to colloquially as

Spitz nevus: clinical features

Spitz nevus, being a nevus, is benign by definition. If there is doubt about the biological potential, a lesion should not be labeled Spitz nevus.

Spitz nevus occurs mainly in white people. As is the case with most benign skin lesions, reliable incidence figures are impossible to obtain, because many do not come to clinical attention. Most are diagnosed in children and adolescents, but a few are encountered beyond middle age. Age is a factor to take into account diagnostically: a Spitz tumor in

Spitz nevus: histologic features

Spitz nevi are junctional, compound, or intradermal proliferations of large melanocytes with increased cytoplasm and enlarged, regular nuclei (Figs. 1 and 2). Shapes vary from epithelioid (rounded or polygonal) to oval and spindle shaped. Epithelioid cells tend to predominate in infancy and early childhood (Fig. 3), whereas spindle cells are most common in adolescence and adulthood (Fig. 4). However, there are many exceptions, and most Spitz nevi contain a mixture of spindle-shaped and

Spitz nevus variants

Through the years, many Spitz nevus variants have been recognized. The common denominator of all of these variants is the key feature of Spitz nevus: increased nevus cell size, with at least some of the architectural features of Spitz nevus outlined earlier.

Desmoplastic Spitz nevus13 is a lesion of late adolescence and of adulthood, and presents as an ill-defined, firm, skin-colored, or light-brown papule, most commonly on the extremities, especially the upper leg. On histology, it is an

Melanocytic BRCA-associated intradermal tumor

Melanocytic brca-associated intradermal tumor (MBAIT) is regarded by many clinicians as an epithelioid Spitz nevus subtype. This lesion deviates in several respects from other Spitz nevus subtypes; the authors think that its inclusion into the group of Spitz nevi has been rightly challenged.26 Nonetheless, a brief discussion is justified here. MBAIT generally presents as a small, shining, smooth-surfaced, reddish or brownish papule, and consists of an entirely or largely intradermal population

Spitzoid melanoma: clinical and histologic features

Some melanomas show a striking resemblance to Spitz nevi.2, 29, 30 Because the degree of resemblance is difficult, if not impossible, to specify reliably, the term spitzoid melanoma does not reflect a well-defined subset of melanomas. Nonetheless, some general remarks can be made, in order to provide some diagnostic guidance to identify them as melanomas.

Implicitly, many of the features of these spitzoid melanomas have been dealt with earlier, because the features indicating malignancy are the

Spitz tumors of uncertain malignant potential

The diagnosis of (spitzoid) melanoma is not difficult when many of the features discussed earlier are present, but diagnostic problems emerge when atypical features are few and present in conjunction with other features that seem to indicate a benign lesion.

A different source of diagnostic uncertainty drives from suboptimal biopsy quality and lack of clinical information. If the specimen is traumatized, or very incomplete, the histologic evaluation is to some degree compromised. The question of

Spitz tumors with incomplete metastatic potential

So far, this article has discussed Spitz nevi, spitzoid melanomas, and lesions for which, either because of intrinsic difficulties in interpretation or because of suboptimal biopsy quality, a diagnosis of nevus or melanoma is impossible, and that are therefore categorized as STUMP or spitzoid SAMPUS.

It is self-evident that, in aggregate, STUMPs, which must be a group of undiagnosable spitzoid tumors that is likely to consist of a mixture of Spitz nevi and melanomas, have a better prognosis than

Novel diagnostic modalities

In recent years, genetic analyses of Spitz tumors have yielded novel data of substantial diagnostic interest.

Conventional melanomas are characterized by high genetic instability and multiple copy number variations when studied by comparative genomic hybridization (CGH). Spitz nevi generally lack chromosomal aberrations besides gains in 11p (15%–20%) or tetraploidy (5%–10%).43 Increases in 11p are sometimes associated with an activating mutation in the HRAS gene, and show an association with the

Nonmelanocytic simulators of Spitz nevus and spitzoid melanoma

A variety of benign and malignant skin tumors consisting of large pale cells with ample cytoplasm may show some resemblance to Spitz nevus. Because none of these shows the involution toward the base that is an important indicator of benignity in Spitz tumors, failure to recognize the nonmelanocytic nature of the lesion may result in overdiagnosis of malignancy. With a small number of notable exceptions (discussed later), diagnostic problems are quickly solved with immune stains. The danger of

Summary

The histologic diagnosis of a Spitz tumor is an especially challenging one, and requires an optimal excisional biopsy as well as detailed clinical information. A confident diagnosis of either nevus or melanoma is not always possible, and diagnostic uncertainty should be communicated in precise and unequivocal terms to the clinician. The differential diagnosis is complicated by the existence of a group of Spitz tumors with limited metastatic potential and that commonly affect a regional lymph

References (57)

  • R.L. Barnhill

    The Spitzoid lesion: rethinking Spitz tumors, atypical variants, 'Spitzoid melanoma' and risk assessment

    Mod Pathol

    (2006)
  • B.C. Bastian et al.

    Molecular cytogenetic analysis of Spitz nevi shows clear differences to melanoma

    J Invest Dermatol

    (1999)
  • B.C. Bastian et al.

    Mutations and copy number increase of HRAS in Spitz nevi with distinctive histopathological features

    Am J Pathol

    (2000)
  • T. Wiesner et al.

    Genomic aberrations in spitzoid melanocytic tumours and their implications for diagnosis, prognosis and therapy

    Pathology

    (2016)
  • D.R. Fullen et al.

    BRAF and NRAS mutations in spitzoid melanocytic lesions

    Mod Pathol

    (2006)
  • C. Requena et al.

    Spitz nevus: a clinicopathological study of 349 cases

    Am J Dermatopathol

    (2009)
  • D.C. Torti et al.

    Spitz nevi arising in speckled lentiginous nevus: clinical, histologic, and molecular evaluation of two cases

    Pediatr Dermatol

    (2011)
  • M.H. Zeng et al.

    Agminated Spitz nevi: case report and review of the literature

    Pediatr Dermatol

    (2013)
  • D. Weedon et al.

    Spindle and epithelioid cell nevi in children and adults. A review of 211 cases of the Spitz nevus

    Cancer

    (1977)
  • C. Paniago-Pereira et al.

    Nevus of large spindle and/or epithelioid cells (Spitz's nevus)

    Arch Dermatol

    (1978)
  • R.J. Reed et al.

    Common and uncommon melanocytic nevi and borderline melanomas

    Semin Oncol

    (1975)
  • A.A. Marghoon et al.

    Spitz and reed nevi. Atlas of dermoscopy

    (2012)
  • H. Kamino et al.

    Eosinophilic globules in Spitz's nevi. New findings and a diagnostic sign

    Am J Dermatopathol

    (1979)
  • R.J. Barr et al.

    Desmoplastic nevus: a distinct histologic variant of mixed spindle cell and epithelioid cell nevus

    Cancer

    (1980)
  • C. Gambini et al.

    Recurrent Spitz nevus. Case report and review of the literature

    Am J Dermatopathol

    (1994)
  • N. Yasaka et al.

    Histopathological evaluation of halo phenomenon in Spitz nevus

    Am J Dermatopathol

    (1995)
  • K.J. Busam et al.

    Pagetoid Spitz nevus. Intraepidermal Spitz tumor with prominent pagetoid spread

    Am J Dermatopathol

    (1995)
  • A.P. Fernandez et al.

    Pagetoid Spitz nevi: clinicopathologic characterization of a series of 12 cases

    J Cutan Pathol

    (2016)
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